Liver-derived plasminogen mediates muscle stem cell expansion during caloric restriction through the plasminogen receptor Plg-RKT

  • Cell Rep. 2024 Mar 4;43(3):113881. doi: 10.1016/j.celrep.2024.113881.
Akshay Bareja  1 ,  David E Lee  1 ,  Tricia Ho  2 ,  Greg Waitt  2 ,  Lauren H McKay  3 ,  Sarah A Hannou  4 ,  Melissa C Orenduff  4 ,  Kristen M McGreevy  5 ,  Alexandra Binder  6 ,  Calen P Ryan  7 ,  Erik J Soderblom  2 ,  Daniel W Belsky  7 ,  Luigi Ferrucci  8 ,  Jayanta Kumar Das  8 ,  Nirad Banskota  9 ,  Virginia B Kraus  10 ,  Janet L Huebner  4 ,  William E Kraus  10 ,  Kim M Huffman  10 ,  Gurpreet S Baht  11 ,  Steve Horvath  12 ,  Robert J Parmer  13 ,  Lindsey A Miles  14 ,  James P White  15
Affiliations
  • 1. Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA; Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, NC 27701, USA.
  • 2. Proteomics and Metabolomics Core Facility, Duke University School of Medicine, Durham, NC, USA.
  • 3. Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, NC 27701, USA; Division of Oral and Craniofacial Health Sciences, Adams School of Dentistry, University of Chapel Hill, Chapel Hill, NC, USA.
  • 4. Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, NC 27701, USA.
  • 5. Department of Biostatistics, UCLA Fielding School of Public Health, Los Angeles, CA 90095, USA.
  • 6. Population Sciences in the Pacific Program (Cancer Epidemiology), University of Hawaii Cancer Center, University of Hawaii at Manoa, Honolulu, HI 96813, USA; Department of Epidemiology, UCLA Fielding School of Public Health, Los Angeles, CA 90095, USA.
  • 7. Columbia University Mailman School of Public Health, New York, NY, USA.
  • 8. Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • 9. Longitudinal Studies Section, Translation Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.
  • 10. Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA; Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, NC 27701, USA; Duke Center for the Study of Aging and Human Development, Duke University School of Medicine, Durham, NC 27701, USA.
  • 11. Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, NC 27701, USA; Duke Center for the Study of Aging and Human Development, Duke University School of Medicine, Durham, NC 27701, USA; Department of Orthopedic Surgery, Duke University School of Medicine, Durham, NC 27701, USA.
  • 12. Computational Biology and Genomics Core, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA; Altos Labs, San Diego, CA, USA.
  • 13. Department of Medicine, Veterans Administration San Diego Healthcare System, San Diego, CA, USA; Department of Medicine, University of California San Diego, La Jolla, CA, USA.
  • 14. Department of Molecular Medicine, Scripps Research, La Jolla, CA 92037, USA.
  • 15. Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA; Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, NC 27701, USA; Duke Center for the Study of Aging and Human Development, Duke University School of Medicine, Durham, NC 27701, USA. Electronic address: [email protected].
PMID: 38442019 DOI: 10.1016/j.celrep.2024.113881
Abstract

An intriguing effect of short-term caloric restriction (CR) is the expansion of certain stem cell populations, including muscle stem cells (satellite cells), which facilitate an accelerated regenerative program after injury. Here, we utilized the MetRSL274G (MetRS) transgenic mouse to identify liver-secreted plasminogen as a candidate for regulating satellite cell expansion during short-term CR. Knockdown of circulating plasminogen prevents satellite cell expansion during short-term CR. Furthermore, loss of the plasminogen receptor KT (Plg-RKT) is also sufficient to prevent CR-related satellite cell expansion, consistent with direct signaling of plasminogen through the plasminogen receptor Plg-RKT/ERK kinase to promote proliferation of satellite cells. Importantly, we are able to replicate many of these findings in human participants from the CALERIE trial. Our results demonstrate that CR enhances liver protein secretion of plasminogen, which signals directly to the muscle satellite cell through Plg-RKT to promote proliferation and subsequent muscle resilience during CR.

Keywords
CALERIE; CP: Metabolism; CP: Stem cell research; MetRS; PAI-1; caloric restriction; liver; muscle; plasminogen; satellite cell; secretome; stem cell.
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-101494
    Temuterkib
    99.93%, ERK1/ERK2 Inhibitor
    target: ERK
    Research Areas: Cancer